Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells
Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells
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DOI：
10.1038/ncb1658
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发表时间：
2007-12-01
影响因子：
21.3
通讯作者：
Sahai, Erik
中科院分区：
文献类型：
--
作者：
Gaggioli, Cedric;Hooper, Steven;Sahai, Erik
癌细胞和间质成纤维细胞的共同侵入共培养物的成像揭示了主导细胞总是成纤维细胞，并且癌细胞在成纤维细胞后面的细胞外基质中的轨道内移动。成纤维细胞产生这些轨迹足以使鳞状细胞癌（SCC）细胞的集体入侵，并需要蛋白酶和力介导的基质重塑。力介导的基质重塑依赖于整合素α 3和α 5，以及成纤维细胞中Rho介导的肌球蛋白轻链（MLC）活性调节，但癌细胞不需要这些因子。相反，癌细胞使用Cdc42和MRCK（肌强直性营养不良激酶相关的CDC42结合蛋白激酶）介导的MLC调节来跟随成纤维细胞产生的轨迹。
Imaging of collectively invading cocultures of carcinoma cells and stromal fibroblasts reveals that the leading cell is always a fibroblast and that carcinoma cells move within tracks in the extracellular matrix behind the fibroblast. The generation of these tracks by fibroblasts is sufficient to enable the collective invasion of the squamous cell carcinoma ( SCC) cells and requires both protease- and force-mediated matrix remodelling. Force-mediated matrix remodelling depends on integrins alpha 3 and alpha 5, and Rho-mediated regulation of myosin light chain ( MLC) activity in fibroblasts, but these factors are not required in carcinoma cells. Instead, carcinoma cells use Cdc42 and MRCK ( myotonic dystrophy kinase-related CDC42-binding protein kinases) mediated regulation of MLC to follow the tracks generated by fibroblasts.